Fibronectin refers to a series of antigenically and structurally similar glycoproteins found in vertebrate blood and connective tissue. Plasma fibronectin is cross-linked to fibrin during blood coagulation by factor XIIIa. Large amounts of fibronectin are synthesized by cultured fibroblasts, and bind to cell surfaces in characteristic fibrillar, fusiform, or punctate structures. After viral transformation, cells continue to synthesize fibronectin but do not bind it to their surfaces. Fibronectin is deposited in blood vessels and basement membranes of all tissues. The structure of fibronectin resembles the structure of factor VIII-related protein, which is synthesized and secreted by endothelial cells. Both proteins are found in or on platelets. Fibronectin also is similar in some respects to alpha-2-macroglobulin, a plasma protease inhibitor. I propose to study the structure and function of the several forms of fibronectin and to make further comparisons fo fibronectin with VIII-related protein and alpha-2-macroglobulin. Plasma fibronectin will be purified and fragmented by chemical treatments or proteolytic enzymes. Cellular fibronectin will be intrinsically radiolabeled and also fragmented. A variety of biochemical and immunological techniques will be used to study the interactions of intact fibronectin and isolated fragments with fibrin, factor XIIIa, cell surfaces, and proteins of connective tissue. Chemical similarities and differences among the several forms of fibronectin will be described. Quantitative methods for analyzing fibronectin in tissue extracts will be developed, and factors determining metabolism of fibronectin in cell culture and in vivo will be identified. Fibronectin and VIII-related protein on platelet surfaces will be radiolabeled, extracted, and identified immunologically. The effects of anti-fibronectin antibody on platelet reactions will be studied. The distribution of fibronectin and VIII-related protein in diseased kidneys will be described.